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89.240.143.77 (talk) synthesis schematic + citations. |
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As with all benzodiazepines, fludiazepam is used recreationally.<ref>{{Cite journal | last1 = Shimamine | first1 = M. | last2 = Masunari | first2 = T. | last3 = Nakahara | first3 = Y. | title = [Studies on identification of drugs of abuse by diode array detection. I. Screening-test and identification of benzodiazepines by HPLC-DAD with ICOS software system] | journal = Eisei Shikenjo Hokoku | issue = 111 | pages = 47–56 | year = 1993 | PMID = 7920567 }}</ref> |
As with all benzodiazepines, fludiazepam is used recreationally.<ref>{{Cite journal | last1 = Shimamine | first1 = M. | last2 = Masunari | first2 = T. | last3 = Nakahara | first3 = Y. | title = [Studies on identification of drugs of abuse by diode array detection. I. Screening-test and identification of benzodiazepines by HPLC-DAD with ICOS software system] | journal = Eisei Shikenjo Hokoku | issue = 111 | pages = 47–56 | year = 1993 | PMID = 7920567 }}</ref> |
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==Synthesis== |
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[[File:Fludiazepam synthesis.svg|thumb|center|700px|Fluorinated analog of diazepam, q.v. Prepn:<ref>E. Reeder et al., {{Cite patent|DE|1136709}}; E. Reeder, L. H. Sternbach, {{US patent|3371085}} (1962, 1968 both to Hoffmann-LaRoche)</ref><ref>L. H. Sternbach et al., J. Org. Chem. 27, 3788 (1962). </ref> Synthesis and pharmacology:<ref>Y. Asami et al., Arzneim.-Forsch. 24, 1563 (1974).</ref>]] |
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(#66) 2-amino-5-chloro-2'-fluorobenzophenone ('''1''') and glycine ethyl ester hydrochloride ('''2''') are reacted together to give 7-chloro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2(1H)-one product ('''3'''). (#74) The product of the last step is reacted with NaOMe followed by MeI to give 7-chloro-1-methyl-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2-one ('''4''') product. |
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(#104)(#105)(#106) |
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A third way is to combine '''6''' and '''2''' → '''4'''. |
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==See also== |
==See also== |
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*[[Benzodiazepine]] |
*[[Benzodiazepine]] |
Revision as of 15:17, 15 August 2015
File:Fludiazepam2D.png | |
Clinical data | |
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AHFS/Drugs.com | International Drug Names |
Pregnancy category |
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Routes of administration | Oral |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | ? |
Metabolism | Hepatic |
Elimination half-life | ? |
Excretion | Renal |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.292.343 |
Chemical and physical data | |
Formula | C16H12ClFN2O |
Molar mass | 302.7 g·mol−1 |
3D model (JSmol) | |
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Fludiazepam, marketed under the brand name Erispan[1][2] is a potent benzodiazepine and 2'-fluoro derivative of diazepam,[3] originally developed by Hoffman-La Roche in the 1960s.[4] It is marketed in Japan and Taiwan in the form of 0.25 mg tablets, making it around 40x more potent than diazepam. It exerts its pharmacological properties via enhancement of GABAergic inhibition.[5] Fludiazepam has 4 times more binding affinity for benzodiazepine receptors than diazepam.[6] It possesses anxiolytic,[7][8][9] anticonvulsant, sedative, hypnotic and skeletal muscle relaxant properties.[10]
As with all benzodiazepines, fludiazepam is used recreationally.[11]
Synthesis
(#66) 2-amino-5-chloro-2'-fluorobenzophenone (1) and glycine ethyl ester hydrochloride (2) are reacted together to give 7-chloro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2(1H)-one product (3). (#74) The product of the last step is reacted with NaOMe followed by MeI to give 7-chloro-1-methyl-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2-one (4) product.
(#104)(#105)(#106)
A third way is to combine 6 and 2 → 4.
See also
- Benzodiazepine
- Diazepam
- Diclazepam (the 2'-chloro-analogue).
- Flunitrazepam (the 7-nitro-analogue).
References
- ^ Su, TP.; Chen, TJ.; Hwang, SJ.; Chou, LF.; Fan, AP.; Chen, YC. (Aug 2002). "Utilization of psychotropic drugs in Taiwan: an overview of outpatient sector in 2000". Zhonghua Yi Xue Za Zhi (Taipei). 65 (8): 378–91. PMID 12455808.
- ^ "Benzodiazepine Names". non-benzodiazepines.org.uk. Retrieved 2008-12-29.
- ^ Neville, GA.; Beckstead, HD.; Shurvell, HF. (Feb 1994). "A Fourier transform-Raman and infrared vibrational study of delorazepam, fludiazepam, flurazepam, and tetrazepam". J Pharm Sci. 83 (2): 143–51. doi:10.1002/jps.2600830207. PMID 7909552.
- ^ US Patent 3299053 -ARYL-JH-L,X-BENZODIAZEPIN-Z(LH)-ONES
- ^ Tsuchiya, T.; Fukushima, H. (Apr 1978). "Effects of benzodiazepines and pentobarbitone on the gaba-ergic recurrent inhibition of hippocampal neurons". Eur J Pharmacol. 48 (4): 421–4. doi:10.1016/0014-2999(78)90169-3. PMID 648585.
- ^ Nakatsuka, I.; Shimizu, H.; Asami, Y.; Katoh, T.; Hirose, A.; Yoshitake, A. (Jan 1985). "Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity". Life Sci. 36 (2): 113–9. doi:10.1016/0024-3205(85)90089-X. PMID 2857046.
- ^ Okada, S.; Ichiki, K.; Tanokuchi, S.; Ishii, K.; Hamada, H.; Ota, Z. (1994). "Effect of an anxiolytic on lipid profile in non-insulin-dependent diabetes mellitus". J Int Med Res. 22 (6): 338–42. PMID 7895897.
- ^ Okada, S.; Ichiki, K.; Tanokuchi, S.; Ishii, K.; Hamada, H.; Ota, Z. (1995). "Improvement of stress reduces glycosylated haemoglobin levels in patients with type 2 diabetes". J Int Med Res. 23 (2): 119–22. PMID 7601294.
- ^ Okada, S.; Ichiki, K.; Tanokuchi, S.; Ishii, K.; Hamada, H.; Ota, Z. (1995). "How blood pressure in patients with non-insulin-dependent diabetes mellitus is influenced by stress". J Int Med Res. 23 (5): 377–80. PMID 8529781.
- ^ Inoue, H.; Maeno, Y.; Iwasa, M.; Matoba, R.; Nagao, M. (Sep 2000). "Screening and determination of benzodiazepines in whole blood using solid-phase extraction and gas chromatography/mass spectrometry". Forensic Sci Int. 113 (1–3): 367–73. doi:10.1016/S0379-0738(00)00226-7. PMID 10978650.
- ^ Shimamine, M.; Masunari, T.; Nakahara, Y. (1993). "[Studies on identification of drugs of abuse by diode array detection. I. Screening-test and identification of benzodiazepines by HPLC-DAD with ICOS software system]". Eisei Shikenjo Hokoku (111): 47–56. PMID 7920567.
- ^ E. Reeder et al., DE 1136709; E. Reeder, L. H. Sternbach, U.S. patent 3,371,085 (1962, 1968 both to Hoffmann-LaRoche)
- ^ L. H. Sternbach et al., J. Org. Chem. 27, 3788 (1962).
- ^ Y. Asami et al., Arzneim.-Forsch. 24, 1563 (1974).
External links
- Template:Ja icon Erispan フルジアゼパム錠,細粒 (PDF) Dainippon Sumitomo Pharma. November 2005.
- Template:Ja icon Official Dainippon Sumitomo Pharma Website